Genetic Variant NM_014228.5:c.1158T>C (chr5-150203737-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014228.5(SLC6A7):c.1158T>C(p.Phe386Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,603,854 control chromosomes in the GnomAD database, including 449,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.71 ( 38295 hom., cov: 28)

Exomes 𝑓: 0.75 ( 410766 hom. )

Consequence

SLC6A7
NM_014228.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.978

Publications

20 publications found

Variant links:

Genes affected

SLC6A7 (HGNC:11054): (solute carrier family 6 member 7) This gene is a member of the gamma-aminobutyric acid (GABA) neurotransmitter gene family and encodes a high-affinity mammalian brain L-proline transporter protein. This transporter protein differs from other sodium-dependent plasma membrane carriers by its pharmacological specificity, kinetic properties, and ionic requirements. [provided by RefSeq, Jul 2008]

SLC6A7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP7

Synonymous conserved (PhyloP=0.978 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A7	NM_014228.5 link	c.1158T>C	p.Phe386Phe	synonymous_variant	Exon 9 of 14	ENST00000230671.7	NP_055043.2	Q99884

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A7	ENST00000230671.7 link	c.1158T>C	p.Phe386Phe	synonymous_variant	Exon 9 of 14	1	NM_014228.5	ENSP00000230671.2		Q99884
SLC6A7	ENST00000524041.1 link	c.1158T>C	p.Phe386Phe	synonymous_variant	Exon 9 of 16	5		ENSP00000428200.1		E5RJL1

Frequencies

GnomAD3 genomes

AF:

0.707

AC:

106948

AN:

151198

Hom.:

38265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.736

Gnomad AMR

AF:

0.769

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.756

Gnomad OTH

AF:

0.726

GnomAD2 exomes

AF:

0.715

AC:

179226

AN:

250756

AF XY:

0.719

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.775

Gnomad ASJ exome

AF:

0.749

Gnomad EAS exome

AF:

0.481

Gnomad FIN exome

AF:

0.621

Gnomad NFE exome

AF:

0.753

Gnomad OTH exome

AF:

0.725

GnomAD4 exome

AF:

0.749

AC:

1087492

AN:

1452538

Hom.:

410766

Cov.:

AF XY:

0.749

AC XY:

541646

AN XY:

723084

show subpopulations

African (AFR)

AF:

0.639

AC:

21205

AN:

33182

American (AMR)

AF:

0.775

AC:

34635

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.747

AC:

19480

AN:

26070

East Asian (EAS)

AF:

0.465

AC:

18417

AN:

39628

South Asian (SAS)

AF:

0.742

AC:

63799

AN:

86008

European-Finnish (FIN)

AF:

0.614

AC:

32723

AN:

53338

Middle Eastern (MID)

AF:

0.789

AC:

4536

AN:

5752

European-Non Finnish (NFE)

AF:

0.769

AC:

848297

AN:

1103798

Other (OTH)

AF:

0.739

AC:

44400

AN:

60096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

12798

25595

38393

51190

63988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20254

40508

60762

81016

101270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.707

AC:

107040

AN:

151316

Hom.:

38295

Cov.:

AF XY:

0.704

AC XY:

52014

AN XY:

73896

show subpopulations

African (AFR)

AF:

0.643

AC:

26466

AN:

41156

American (AMR)

AF:

0.769

AC:

11719

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

2616

AN:

3460

East Asian (EAS)

AF:

0.487

AC:

2478

AN:

5092

South Asian (SAS)

AF:

0.734

AC:

3515

AN:

4786

European-Finnish (FIN)

AF:

0.626

AC:

6532

AN:

10436

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.756

AC:

51286

AN:

67828

Other (OTH)

AF:

0.725

AC:

1529

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1520

3040

4560

6080

7600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.741

Hom.:

35481

Bravo

AF:

0.713

Asia WGS

AF:

0.662

AC:

2299

AN:

3476

EpiCase

AF:

0.768

EpiControl

AF:

0.765

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.7

(source)

DANN

Benign

0.53

PhyloP100

0.98

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over